title: Eating and hypothalamus changes in behavioral-variant frontotemporal dementia.
abstract: OBJECTIVE
  Behavioral-variant frontotemporal dementia (bvFTD) is a progressive neurodegenerative brain disorder, clinically characterized by changes in cognition, personality, and behavior. Marked disturbances in eating behavior, such as overeating and preference for sweet foods, are also commonly reported. The hypothalamus plays a critical role in feeding regulation, yet the relation between pathology in this region and eating behavior in FTD is unknown. This study aimed to address this issue using 2 complementary approaches.
  
  
  METHODS
  First, 18 early stage bvFTD patients and 16 healthy controls underwent high-resolution structural magnetic resonance imaging and assessment of eating behavior. Hypothalamic volumes were traced manually on coronal images. Second, postmortem analyses of 12 bvFTD cases and 6 matched controls were performed. Fixed hypothalamic tissue sections were stained for a cell marker and for peptides regulating feeding behaviors using immunohistochemistry. Stereological estimates of the hypothalamic volume and the number of neurons and glia were performed.
  
  
  RESULTS
  Significant atrophy of the hypothalamus in bvFTD was present in both analyses. Patients with high feeding disturbance exhibited significant atrophy of the posterior hypothalamus. Neuronal loss, which was observed only in bvFTD cases with Tar DNA protein-43 deposition, was also predominant posteriorly. In contrast, orexin (hypocretin), neuropeptide Y, cocaine- and amphetamine-regulating transcript, and vasopressin-containing neurons that regulate appetite were spared in posterior nuclei known to participate in feeding regulation.
  
  
  CONCLUSIONS
  Degeneration and consequent dysregulation within the hypothalamus relates to significant feeding disturbance in bvFTD. These findings provide a basis for the development of therapeutic models.
authors.affiliation: Neuroscience Research Australia, Sydney, Australia. o.piguet@neura.edu.au
authors.forename: Olivier
authors.initials: O
authors.lastname: Piguet
authors.forename: Asa
authors.initials: A
authors.lastname: Petersén
authors.forename: Bonnie
authors.initials: B
authors.lastname: Yin Ka Lam
authors.forename: Sanaz
authors.initials: S
authors.lastname: Gabery
authors.forename: Karen
authors.initials: K
authors.lastname: Murphy
authors.forename: John R
authors.initials: JR
authors.lastname: Hodges
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
mesh_terms: D000368:Aged; D001066:Appetite / Q000502:physiology; D001284:Atrophy / Q000473:pathology; D002452:Cell Count; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D005518:Food Preferences / Q000502:physiology; D057180:Frontotemporal Dementia / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007031:Hypothalamus / Q000473:pathology* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D009929:Organ Size